A 6-week-old, otherwise healthy boy presented to the dermatology clinic for evaluation of an eruption involving his scalp, face, and trunk. The truncal lesions had been present for several weeks, and the facial and scalp lesions were noticed 5 days prior to presentation. The eruption was asymptomatic without scratching or discomfort noted by his mother.
Past medical history was remarkable for preterm delivery due to maternal hypertension during pregnancy. The infant was thriving and gaining weight appropriately. There was no family history of cutaneous or autoimmune disease. No one in the family had a recent tinea infection.
On physical exam, he was a well-appearing, vigorous infant. There were multiple erythematous papules and annular plaques involving his left pre-auricular and post-auricular areas, scalp, upper chest, and right abdominal wall ( Figures 1 and 2 ). No other cutaneous or mucus membrane lesions were noted. His cardiac, lung, and abdominal exams were normal.
Neonatal lupus erythematosus (NLE) is an acquired condition that occurs in infants born to mothers with autoimmune diseases. The disease is caused by transplacental passage of maternal autoantibodies, most commonly antiRo (SSA) and anti-La (SSB) antibodies. Importantly, about half of mothers of affected infants are asymptomatic at the time of delivery, and about half of these originally asymptomatic mothers go on to develop autoimmune disease, most commonly Sjogren syndrome, systemic lupus erythematosus, or undifferentiated autoimmune syndrome. 1,2 Therefore, NLE is most important for asymptomatic mothers who are at risk. The incidence of NLE is approximately one in 12,500 to 20,000 live births, but the true incidence is still not known because of under-diagnosed cases. Girls are slightly more affected than boys. 3
This patient’s diagnosis was made through a combination of clinical features, a positive antinuclear antibody titer of 1:640 speckled pattern, and strongly positive autoantibodies to anti-U1RNP. The remaining laboratory studies were normal, including a CBC, hepatic function panel, antiphospholipid antibodies, and SSA and SSB antibodies. An electrocardiogram and echocardiogram were also normal. His cutaneous lesions resolved without residual atrophy over the course of 2 to 3 months. His mother was subsequently diagnosed with subacute cutaneous lupus erythematosus.
The most common clinical manifestations in infants affected by NLE are cutaneous lesions and cardiac disease. The most serious complication of NLE is complete heart block. 4,5 Hematological abnormalities reported include pancytopenia, leukopenia, thrombocytopenia, and Coombs positive or negative hemolytic anemia. Liver involvement may include hepatomegaly, abnormal liver function tests, and rare cholestatic disease and liver failure. 6 Most often, hepatic or hematological findings are transient. Splenomegaly, lymphadenopathy, and central nervous system and pulmonary diseases can also be noted in these patients. 3
Approximately 50% to 70% of all newborns with NLE will show cutaneous manifestations, with onset usually by a few weeks of age and fading within the following 6 months, coincident with the clearance of maternal antibodies from the child’s circulation. The eruption is noted at birth in few cases, and many affected children will not develop a rash until after exposure to UV light. In a cohort of 57 infants, the eruption was recognized at a mean of 6 weeks and lasted an average of 17 weeks. 2 Development of new lesions after 3 months of life is rare.
The eruption is usually comprised of erythematous annular lesions with slight central atrophy and raised margins, most commonly localized on sun-exposed areas, particularly on the head and neck, typically periorbital in distribution, less commonly on the trunk, and extremities. 2,3 The periorbital distribution has been termed ‘raccoon eyes.’ A variety of cutaneous manifestations have been reported, including annular lesions, discoid lesions, scaly atrophic macules and patches, pitted atrophic scars, reticulated vascular lesions, and telangiectasia. In one study, skin lesions reported were erythematous patches (91.7%), subacute cutaneous lupus erythematosus (SCLE) lesions (50%), petechiae (41.7%), persistent cutis marmorata (16.7%), and discoid lesions (8.3%). 3 The differential diagnosis includes the following: annular erythema of infancy, erythema annulare centrifugum, seborrheic dermatitis, fungal infections such as tinea corporis, and Sweet syndrome. Most cutaneous lesions resolve without sequelea, but residual changes may include dyspigmentation, atrophy, telangiectasia, and scarring.
Of note, NLE is the most frequent cause of congenital heart block. It occurs in 15% to 30% of affected patients. 3 This is caused by in utero inflammation, fibrosis, and calcifications of the atrioventricular or sinoatrial nodes. This condition is usually noted on physical examination as bradycardia at birth but may be recognized with ultrasonography in utero. Most often, congenital heart block in patients with NLE is irreversible, even with systemic glucocorticoid therapy. Pacemaker implantation is frequently necessary. 7
Several studies have established the association between SSA, SSB, and NLE. In studies of neonates born to mothers with known SSA antibodies, approximately 10% to 20% developed cutaneous findings of NLE, 1% to 2% had heart block, and 27% had other laboratory abnormalities. 4,8 Retrospective evaluations of mothers who gave birth to infants with complete heart block often reveal positivity for SSA and SSB antibodies. 5 The SSA antibodies are likely the causative antibody for heart block by binding to cardiac myocytes, causing injury to the conduction system. 8 Of note, positive anti-U1RNP antibodies are usually associated with cutaneous lesions of NLE without cardiac or systemic abnormalities. 3
In neonates with suspected NLE, the recommended work-up is as follows: serologic evaluation including antinuclear antibody, anti-U1RNP, SSA and SSB, CBC with platelet count, liver function tests, and an electrocardiogram. There are no specific diagnostic criteria for NLE. The diagnosis is made by the presence of typical cutaneous lesions; systemic manifestations such as heart block and/or hepatic or hematologic manifestations; and confirmatory laboratory studies, including anti-U1RNP, SSA, and SSB antibody tests of the infant and mother.
Typical histopathologic findings in NLE are vacuolar alterations at the dermoepidermal interface and adnexal structures. Some patients present with SCLE/urticaria-like lesions that have superficial and deep perivascular and periadnexal lymphocytic infiltrates without epidermal alteration. 9 Most often, this is a clinical diagnosis confirmed by laboratory findings, and a biopsy is not needed.
Low-potency topical steroids and strict sun protection are the mainstays of therapy for treatment of cutaneous NLE. 3 Children with NLE may be at increased risk for developing an autoimmune and/or rheumatic disease, although this is rare. In a study that included 49 children with NLE followed to at least the age of 8, six of the children (12%) developed a well-defined systemic rheumatic and/or autoimmune disease. 10 Although the health of the affected child may be permanently impacted, the diagnosis of NLE is also of utmost importance for maternal health, and these mothers must be evaluated and followed closely.